Glycogenesis Flashcards
Can fiber be digested by humans? What is fiber made out of?
Fiber is in many cases made of carbohydates. bacteria in our gut biome break down the fiber
Difference in structure between starch, glycogen and cellulose
startch: molederately branched, glycogen: high branceed,
cellulose: unbranced
Why cant we break down cellculose
we dont have the beta glucose 1-4
what bonds can we breakdwon
alpha glucose 1-4 and alpha glucsoe 1-
What is starch? storage form? Structure?
Most improtant source of carbohydrates in the human diet. Storage form of carbohydrates in plants (in the form of granules)
Starch is a mixture of 2 polymers: amylose (linear) and amylopectin (branched)
What is cellulose? storage form? Structure?
- structureal compoenet of plant cell wall. most abundant of all carbohydrates
structure simialr to amylose but different glycosidic bond. humans cant metabolize cellulose
What is glycogen? storage form? Structure?
energy rserve carbohydrate in animals and fungi
strucutally simialr to amylopeptic but more highly branched
why is it faster/ more convenient to gain energy via glycogen
despite lipids have more energy than glycogen, it takes longer to break down lpids, need to be breoken down to acetyl coA.
Lipids need aerobic respiration, but for starch, we can have anaerobic respiration
Core of the glycogen molecule is the protein
glycogenin
What is glycogen? where is it prsent?
how immediate is can it provide nergy?
Glygogen: highly branched homopolymer of glucose.
It is present in all tissues (particularly in muscles and liver)
Most immediately available large-scale storage of metabolic energy
What is the structure of glycogen? Purpose of branching?
Alpha 1-4 and alpha 1-6 glycosidic bonds between monomers.
Most glucose residues are linked by alpha 1-4.
Branches every tenth residue.
The branching increases glycogen solubility and allows it to be breakdown more quzil
Where is glycogen predominantly present
liver nad muscle (liver > muscle)
Glycogen occurs in small ____
Granules
glycogen is not as neergy rich as fatty acids. Why do animals store it for energy?
Glycogen serves as a buffer to maintain blood glucose levels. the glucose from glycogen is readily mobilized. Unlike fatty acids, the release of glucose can provide neegyin the absence of oxygen.
=> maintian blood-glucose levels -> metabolism is regulated by insulin and glucagon
What is the formula for glycogen synthesis?
Glycogen(n) + UDP-glucose -> glycogen(n+1) + UDP
What is the formula for glycogen degradation?
glycogen(n+1) + pi -> glycogen (n) + glucose-1-phosphate
What enzymes are needed for glycogen synthesis?
UDP-gluclse pyrophosphorylase
Glycogen synthase
Branching enzyme
What is the precurser for glycogen syntheiss?
How is the C1 of UDP-glucose activated
Precusros is UDP-glucose (not glucose-1-phosphate)
Glycogen syntheiss requires an activated precurosor.
C1 of UDP-glucose is activated because its OH group is esterified to the dthe diphosphate of UDP
What are the steps to glycogen synthesis and the enzymes
- Activcation of glucose:
UDP-glucose pyrophosphorylase
UDP-glucose is the activated intermediate in glycogen syntehsis
2. Extension of the chain: glycogen synthase
New glycosyl units are added to non-reducing end of glycogen to form alpha1-4 glycosidic bond
- Brnaching
Branching enzyme
Creates a branch by breaking off an alpha 1-4 bond and forming an alpha 1-6 bond. it transfers a block of seven or so to a more residue site
What is the regulatory step in glycogen synthesis?
Glycogen synthase
Humans have 2 isoforms of glycogen synthase?
1 specific to muscles and the other to tissues
Why must glycogen be broken down? liver/muscle
Muscle glycogen stores are mobilized to provide energy for muscle contraction.
The liver breaks down glycogen and releases glucose to the bloodstream to provide energy for the brain and red blood cells.
What enzymes are needed for breakdown of glycogen?
- Phosphorylase
- Transferase
- Debranching enzyme
- Phosphoglucose mutase
What are the steps to glycogen break down.
- Glycogen phosphorylase cannot cleave near branch points and can only cleave alpha1-4-glycosidic bonds. Releases glucose 1-phosphate (keeps on cleaving until it encounters/close to a brnaching point)
- A transferase shifts a small oligosaccahride near the branch point to a nearby chain, making the glucose moities accessible to the phosphorylase
- A debranching enzyme (alpha1-6 glucosidase) then cleaves at the branch point releasing a free glucose
- Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate
Which gives more energy? glucose-1-P or glucose?
glucose-1-P?
What is the regulatory step in glycogen break down
Phosphorylaese
What is glycogen phosphorylase? WHat is the general formula ?
Degrades glycogen from the non-reducing ends of the glycogen molecule.
The phosphorylase catalyzes a phosphorylsis reaction that yeidls glucose 1- phosphate
Glycogen (n) + Pi <-> glucose-1-phosphate + glycogen (n-1)
How does glycogen go to glucose? elaborate on phosphoglucomutase
Glucose-1-phosphate must be converted into glucose-6-phosphate to enter metbaolic mainstream. Done w the help of phosphoglucomutase.
Liver needs to release glucose into the blood during muscular activity and fasteing. Glucose-6-Phoshpahte (in the lumen of ER), cleaves the phsophoryl group to form free glucose and Pi.
What fates does glucose-6-P have?
glycoslysis in the muscle, brain
liver: glucose-6-phosphatase converts glucose-6-P -> glucose
How is glycogen metabolism regulated differently by allosteric control and hormonal control?
-Allosteric control: responds to metabolites that signal the energy needs of the cell. allows adjustment of enzyme activity to meet the needs of the cell.
- Hormonal control: stimulates a cascade that leads to the resersible phosphoyrlation of enzymes (altering kinetic properties)
Allows adjustmnts to meet the needs of the entire organism
What are the regulators for glycogen phosphorylase
(-) Glucose
(+) AMP, Ca2+
What are the regulators for Glycogen synthase
(+) Glucose-6-P
Liver phosphorylase is insensitive to..
regulation by AMp and calcium
Glucose-6-P is also a regulator for
(-) regulator for hexokinase in glycolysis
Glycogen synthesis in liver and muscle is for? how is it differnet?
Liver maintains glucose homeostasis fo organism
Muscle uses glucose to produce energy for itslef
What regulates glycogen phosphorylase in the liver?
Glucagon
What regulates glycogen phosphorylase in the muscle
AMP, Ca2+
How is glycogen degradation by tissue regulated differently by the liver and the muscle
Liver glycogen phosphorylase produces the glucose for use by other tissues. Liver phosphorylase is prepared to generate blood glucose unless signaled otherwise:
(+) Glucagon
Muscle glycogen phosphorylase is regulated by intracellular energy charge
(+) AMP, Ca2+
Glycogen synthase exists in 2 forms that is controlled by
covalent modification + allosteric regulaation
Glycogen sysnthase is active when (P/no P)
not phosphorylated
GLycogen synthease is inactive when
its phosphorylated
Glycogen synthase is also regulated by allosteric regulation of?
allosteric regulation of glycogen synthase b by the positive regulator glucose-6-P
Phosphorylase is regulated by
allosteric effectors and reversible phosphorylation
Which is the more active phosphorylase?
Phospohorylase a is phosphorylarated -> more active. Actie T state
What is the inactive phosphorylase?
Phosphorylase b is not phosphorylated. Less active, T state
Whats the default state of phosphorylase in muscle?
Not phsophorylated
How is glycogen phosphorylase regulated in muscles?
at rest, glycogen phosphoyrlase is not phosphorylated, in the inactive b form.
When its low energy, high concenteration of AMP favors transition to R state.
Glucose-6-P and ATP stabilize the T state
What is the default state of phosphorylase in the liver
a
what allosteric regulators stabilize the T state of phosphorylase?
ATP and glucose-6-P
What allosteric regulators stabilize the R state
AMP
How does glucagon and epinephrine mediate the coordination of pathways?
GLucagon(liver) (low blood glucose concentration)
-> glycogen breakdown
-> phosphorylation of of phosphorylase -> make it active
Epinephirne (muscle)( fear or the excitement of exercise will cause the release)
-> glycogen break down
-> phosphorylation of phosphorylase -> make it active
How does insulin mediate the coordination of pathways?
Insulin(high blood-glucose concentration)
-> glycogen synthesis
glycogen synthase is dephosphorylated -> make it active
How are the different sources of fuel used for energy? (in what order)
Use the little ATP have in stored -> creatine -> glucose -> glycogen
When fasting, what are the 2 processes the liver can do to get glucose in the blood stream?
Glucagon ->
Glycogen -> glucose
Lactate -> glucose
When you are fasting, in the liver, _____ will induce what?
Glucagon. Glycogen breakdown and gluconeogenesis
When you are exercising,in muscles ____ will induce
epinephirne. glycogen breakdown and glycolysis
How is glycogen synthase regulated
Insulin -> (Phosphorlltion of IRS-P) -> triggers a cascade that leads to phsophorylation and activation of protein kinases
-> phosphorylation leads to inactivation of glycogen synthase kinase (GSK)
-> if the kinase is inactive -> protein phosphophatase-1 (PP1) can remove the phosphoryl group of glycogen synthase -> activating the enzyme
What are the parts to the regulation of glycogen synthase
dephosphorylated glycogen synthase -> active, form a
phosphorylated glycogen synthase -> unactive, form b
interconversion is controlled by:
glycogen synthase kinase (GSK)
protein phosphatase-1 (PP-1)
adidtionally, glucose-6-p (positive regulator) allosterically regulates glycogen synthase b
Fill in the blanks:
PP1 ______ glycogen synthesis
GSK ______ glycogen synthesis
Insulin ____glycogen syntheiss
activates
inactivates
activates
How does regulation of glycogen phosphorylase work?
Perception of epinephrine or glucagon
-> (cyclic AMP) signalling cascadde that leads to activation of protein kinase A (PKA) -> PKA phosphorylates phosphorylate kinase -> phosphorylate kinase activations glycogen phosphoryate (phosphorylate a) by phosphorylation -> glycogen degradation
What are the pieces to glycogen phosphorylatse
2 forms:
phosphorylase a -> active -> phosphorylated
phosphorylase b -> inactive -> non-phsohphoryualted
interconversion is controlled by phosphorylase kinase
protien phosphatase 1
Phosphorylase kinase is controlled by PKA
Elaborate on the cAMP cascade
- Binding of hormone to 7TM receptor in target cells, triggers interaction with the G protein
- GTP-bound G protein activates adenylate cyclase, which catalyzes the formation of cAMP (cyclic AMP), which activates protein kinase A (PKA)
- PKA then phosphorylates phosphorylase kinase, which phosphorylates phosphorylase b
- PKA and GSK add phosphoryl group to glycogen synthase
How are glycogen breakdown and synthesis reciprocoally regulated by PKA
Glucagon activates liver phosphorylase:
PKA activcates phsophorylase kinase (via phosphorylase)
phosphorylase kinase activates phsophorylase
Glucagon inactivates glycgoen syntehsis
PKA phosphorylase glycogen synthase -> makes it inactive
How is glycogen breakdown and synthesis regulated by PP1. After a meal or when at rest
PP1 -> glycogen breakdown is inhibited.
pphosrylase kinase is inactive (not phosphorylated)
phoshorylase not active (not phsophorylated)
-> phosphoylase in inactive
PP1 -> glycogen syntheiss is stimulated
glycogen synthase is active
How does glucagon activate liver phosphorylase?
How does glucagon inactivate glycogen synthase?
by stimutlating PKA -> .. -> phosphoyrlation of phsphorylase -> activate break down
by stimulating PKA -> phsophorylation of glycogen synthase -> inactvates synthesis
How does insulin inactvatie liver phosphorylase?
How does insulin stimulate glycogen synthesis?
by stimulating PP1. making phosphorylase dephosphoryalted -> inactivating breakdown
Insulin stimulates glycogen synthase by stimulating PPP1
making glycogen synthase active via dephosphorylatio
PP1 removes phosphaetes from
- glycogen phsophorylase
- glycogen synthase
PKA adds phosphates to
- phosphorylase kinase -> glycogen phosphorylase
- glycogen synthase
consicely explain the insulin cascade
Insulin -> PP1 -> inhibits glycogen break down -> stimulates glygogen formation
consicely explain the glucagon cascade
glucagon/epinephrine -> PKA -> simutlates glycogen breakdown
inhibits glycogen formation
how is PFK-2/FBPase-2 regulated in the liver by hormones?
Glucagon stimulates phosphorylation -> simulates glucogenogenssi
Insulin stimuates dephosphorylation -> stimutlates glycolsysis
how is the phosphorylation of PFK-2 and FBPase-2 regulated in the liver?
Insulin stimulates protien phosphotatse -> dephosphorylation of PFK-2/FPB-2
Glucagon stimualetes protein kinase A -> leads to phospphoruation of PFK-2/FPB-2
What is glycogen storage disease
A metabolic disorder caused by enzyme deficiencies affecting glycogen synthesis or breakdown
What is a pomp disease
it is an iretited disorder caused by a buildup of glycogen in the bodys cells. Can rupture and affect neighboring cells.
The accumulation of glycgoen in certain. organs and tissues , like the heart, skeletal muscles nad central nervous sytem impairs their ability to function normally
What causes Pomp disease
Normally, the body uses GAA (encoding glucosidase to break down glycogen). mutations in the GAA
What does Pomp disease cause
Fasting hypoglycemia (low blood sugar)
How to resolve it? with uncooked corn starch and continuous feedbing overnight
